1,721,013 research outputs found
Sviluppo di modelli per lo studio dei processi di ruscellamento ed infiltrazione presso il campo ex-marcita
No full textMIR-296 AND ITS TARGET SCRIB IN BREAST CANCER
Full text linkI microRNA (miRNA) sono piccoli RNA non codificanti che regolano negativamente l'espressione di numerosi mRNA a livello post-trascrizionale. I microRNA sono coinvolti in svariati processi fisiologici (sviluppo, crescita e differenziazione cellulare, apoptosi, etc) e la loro espressione aberrante è stata riportata in vari tipi di malattie, compresi i tumori.
miR-296 svolge un ruolo importante in diversi tipi di cellule, controllando l'angiogenesi, il differenziamento delle cellule staminali, il potenziale oncogenico e la motilità. Queste ultime due funzioni sono potenzialmente mediate dall’ inibizione di un suo target, Scrib, una proteina citoplasmatica coinvolta nel mantenimento della polarità apico-basale e nella motilità delle cellule. Nei tumori il ruolo di miR-296 e del suo target Scrib rimane ancora dibattuto e pochi dati sono disponibili riguardo i carcinomi della mammella.
Data la partecipazione di miR-296 nella regolazione di processi fisiologici di solito alterati nei tumori, abbiamo deciso di valutare i livelli di espressione di miR-296 mediante Real Time PCR e del suo target Scrib mediante immunoistochimica in un'ampia serie di tumori mammari per individuare eventuali correlazioni con i parametri clinici e patologici, utili a fini prognostici e / o predittivi, e per chiarire il ruolo di questo miRNA e del suo target nella tumorigenesi mammaria.
Infine, per valutare se modificando i livelli di miR-296 si potevano avere effetti sulla crescita neoplastica, abbiamo iniettato cellule tumorali mammarie (MDA-MB 231), impiantate in un modello di xenotrapianto, con un precursore di miR-296 o una molecola di controllo e monitorato nel tempo la crescita tumorale.
I nostri dati mostrano che i livelli di miR-296 sono costantemente ridotti nei carcinomi della mammella rispetto al parenchima mammario sano. Inoltre, nel sottogruppo di pazienti con metastasi a distanza, è stata osservata una correlazione significativa tra la riduzione dei livelli di miR-296 e la disseminazione precoce del tumore.
Per quanto riguarda il target di miR-296, Scrib è risultato espresso in un numero maggiore di casi nei carcinomi mammari rispetto al parenchima normale e con un’intensità maggiore.
L’iniezione diretta di miR-296 in cellule di carcinoma mammario umano impiantate in un modello di xenotrapianto ha inoltre ridotto la crescita del tumore rispetto ai controlli.
I nostri dati confermano il coinvolgimento di miR-296 nella tumorigenesi mammaria, in particolare, una riduzione significativa dei suoi livelli è stata osservata nei carcinomi rispetto ai controlli normali e la sua forzata riespressione nel modello di xenotrapianto è risultata efficace nel rallentare la crescita tumorale. Inoltre, l’osservazione che nel gruppo dei pazienti con metastasi a distanza esiste una correlazione significativa tra riduzione dei livelli di miR-296 e lo sviluppo precoce delle metastasi mette in evidenza il ruolo di miR-296 come regolatore della migrazione e dell'invasività cellulare.
Con queste premesse, miR-296 potrebbe rappresentare un nuovo target per la progettazione di farmaci mirati, atti a ripristinare i livelli di miRNA e ad indurre effetti anti-neoplastici.microRNAs (miRNAs) are small non-coding RNAs which negatively regulate the expression of several mRNAs at post-transcriptional level. miRNAs are involved in multiple physiological processes (development, differentiation and cell growth, apoptosis, etc.) and their aberrant expression has been reported in several types of diseases, including tumors.
miR-296 plays important roles in different cell types and cellular pathways, regulating angiogenesis, stem cell differentiation, cell tumorigenic potential and motility. These latter two functions are potentially mediated by inhibition of one of its target, Scrib, a cytoplasmic protein involved in apico-basal cell polarity maintenance and in cell motility. In tumors, the role of miR-296 and of its target Scrib still remains debated, and scarce data are available in breast carcinomas.
Given the role of miR-296 in control of physiological processes normally deregulated in tumors, we aimed to evaluate the expression levels of miR-296 by Real Time PCR and of its target Scrib by immunohistochemistry, in a large series of breast cancers to identify any correlations with clinical and pathological parameters, useful for prognostic and/or predictive purposes, and to clarify the role of this miRNA and its target in mammary tumorigenesis.
Finally, to evaluate if modification of miR-296 levels could have effects on neoplastic growth, we injected breast cancer cells (MDA-MB 231), implanted in a mouse model, with a precursor of miR-296 or a control molecule monitoring tumor growth in time.
miR-296 levels were consistently reduced in human breast cancer tissues compared with non-neoplastic mammary parenchyma. In the subgroup of patients with distant metastases, a significant correlation between reduced miR-296 levels and earlier spread of cancer was detected.
Regarding miR-296 target, breast cancers displayed higher levels of Scrib compared to normal parenchyma, and with a greater intensity.
Direct injection of pre-miR-296 into tumoral masses of a xenograft model significantly decreased tumor growth.
Our data confirm the involvement of miR-296 in breast cancer tumorigenesis, in particular, a significant reduction is observed in infiltrating carcinomas compared to normal controls and experimentally induced restoration of its levels in xenograft assays resulted effective in slowing tumor growth. Furthermore, our observation in the group of patients with distant metastases, showing a significant correlation between reduced miR-296 levels and the earlier onset of distant metastases, highlights the role of miR-296 as a regulator of cell migration and invasion.
With this background, miR-296 could represent a new therapeutic approach and provide a scientific rationale for the design of new drugs with molecular target, appropriate to restore the levels of miRNAs and induce anti-neoplastic effects
Una procedura per la redazione di carte di pericolosita’ di alluvione nelle aree di conoide
No full textIdentification of flow parameters for a regional multi-layered aquifer with the differential system method
No full text[Review of 87 cases of scoliosis surgically treated].
No full textThe authors compared the results and complications in surgical treatment of idiopathic scoliosis with Harrington's rod instrumentation with subtrasversal wires in dorsal treat. A research on 87 cases operated on for idiopathic scoliosis from 1987 to 1995 is carried out. The 87 cases include 65 females and 25 males, 16 years old in average (range, 11 to 30). The curvature in Cobb's degrees and rotation of vertebrae with Raimondi's method on radiographs take just before, 15 days later and an year later on operation was measured. The patients have been divided into two groups: the first of 77 patients operated with Harrington's rod instrumentation; the second of 10 patients operated with Harrington's rod instrumentation and subtrasversal wires. In a general analysis without taking in to consideration the type and the seriousness of curvature it was obtained a better correction and derotation of vertebrae in patients of second group. The same group with wires had obtained a better correction and derotation of vertebrae in dorsal scoliosis from 40 degrees to 60 degrees and in the double scoliosis, while the first group obtained better results in dorsal scoliosis from 60 degrees to 80 degrees and in derotation of vertebrae on dorsal treat of double scoliosis. One case of pseudarthrosis in every group was observed. Any neurological complication were observed. The conclusions is drawn that the application of subtrasversal wire improves the Harrington's technique for the correction and derotation of dorsal and double scoliosis without neurological complications sometimes present with subliminar wires
Identification of hydrodynamic parameters for a regional multilayered aquifer with the DS method
No full textThe DS method is applied to a regional aquifer which consists of two confined aquifers separated by a semipermeable layer. We use the results of a previously calibrated forward model of this real aquifer system as data for the DS method and we reconstruct the spatial distribution of the aquifers transmissivity and the leakage coefficient
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
- …
